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分析炎症性肠病中鼠类和人类 Treg 亚群。

Analysis of murine and human Treg subsets in inflammatory bowel disease.

机构信息

Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, Liaoning 110001, P.R. China.

Allergy and Clinical Immunology Research Centre, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.

出版信息

Mol Med Rep. 2017 Sep;16(3):2893-2898. doi: 10.3892/mmr.2017.6912. Epub 2017 Jul 4.

Abstract

Previous studies have indicated that regulatory T cells serve essential roles in maintaining intestinal homeostasis, however, the role of different Treg subsets in modulating inflammatory bowel disease has still not been addressed clearly. In the present study, the authors measured the percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs, Foxp3‑ IL‑10+ TGF‑β‑ induced Tregs, CD127‑ induced Tregs and CD8+ Tregs at different time points in DSS‑induced experimental colitis model in murine lamina propria lymphocytes, mesenteric lymph node and peripheral blood. In addition, the authors compared the frequency of four Treg subsets in patients diagnosed of ulcerative colitis at different stages with enrolled healthy controls. The percentage of Foxp3+ IL‑10+ TGF‑β+ natural Tregs decreased in acute stage of both human and mice was observed, but proliferated significantly during remittent stage. Foxp3‑ IL‑10+ TGF‑β‑ inducible (i) Treg and CD127‑ iTreg was observed as being significantly decreased percentage in LPL at 4 and 7 days, the frequency of Foxp3‑ IL‑10+ TGF‑β‑ iTreg cells became decreased and CD127‑ iTreg only slightly increased at the chronic stage following DSS induction. However, the proportion of both Foxp3‑ IL‑10+ TGF‑β‑ iTreg and CD127‑ iTreg was nearly unchanged in human IBD. Although intestinal inflammation decreased the percentage of CD8+ Tregs, it remained lower in the remittent stage of human IBD. Only enhanced proliferation of lamina propria lymphocytes‑derived CD8+ Treg was reported at 7 days in dextran sodium sulfate‑induced murine colitis. The results demonstrated that Foxp3+ IL‑10+ TGF‑β+ natural Tregs may serve an essential role in exhibiting suppressive and protecting from immune‑related mucosal injury during chronic stage in inflammatory bowel disease.

摘要

先前的研究表明,调节性 T 细胞在维持肠道稳态方面发挥着重要作用,然而,不同 Treg 亚群在调节炎症性肠病中的作用仍未得到明确阐述。在本研究中,作者在小鼠固有层淋巴细胞、肠系膜淋巴结和外周血的 DSS 诱导的实验性结肠炎模型中,测量了不同时间点 Foxp3+IL-10+TGF-β+天然 Treg、Foxp3-IL-10+TGF-β-诱导的 Treg、CD127-诱导的 Treg 和 CD8+Treg 的百分比。此外,作者比较了不同阶段溃疡性结肠炎患者和纳入的健康对照者这四种 Treg 亚群的频率。在人类和小鼠的急性期均观察到 Foxp3+IL-10+TGF-β+天然 Treg 的百分比下降,但在缓解期显著增殖。在第 4 天和第 7 天,LPL 中观察到 Foxp3-IL-10+TGF-β-诱导(i)Treg 和 CD127-iTreg 的百分比显著降低,在 DSS 诱导后慢性期,Foxp3-IL-10+TGF-β-iTreg 细胞的频率降低,而 CD127-iTreg 仅略有增加。然而,在人类 IBD 中,Foxp3-IL-10+TGF-β-iTreg 和 CD127-iTreg 的比例几乎没有变化。尽管肠道炎症降低了 CD8+Treg 的百分比,但在人类 IBD 的缓解期仍然较低。在葡聚糖硫酸钠诱导的小鼠结肠炎中,仅报道了固有层淋巴细胞衍生的 CD8+Treg 在第 7 天的增殖增强。结果表明,在炎症性肠病的慢性期,Foxp3+IL-10+TGF-β+天然 Treg 可能在发挥抑制作用和保护免疫相关黏膜损伤方面发挥重要作用。

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